Allosteric PROTACs: Expanding the Horizon of Targeted Protein Degradation
University of Dundee · Cancer Targeted Technology (United States)
Abstract
Proteolysis-targeting chimeras (PROTACs) have transformed the concept of chemical intervention in biological systems by co-opting the ubiquitin-proteasome system to selectively degrade proteins. A key promise of this modality is that proximity alone─not inhibition─is required, allowing binding anywhere on the protein surface to trigger degradation. Yet despite this conceptual freedom, most PROTACs to date have been built from orthosteric inhibitors. The use of allosteric or functionally silent ligands remains a largely untapped opportunity. In this Perspective, we spotlight pioneering efforts in allosteric PROTAC design and explore how such strategies could unlock improved outcomes for target selectivity,…
Citation impact
- FWCI
- 75.25
- Percentile
- 100%
- References
- 109
Authors
3Topics & keywords
- Allosteric regulation
- Model system
- Protein–protein interaction
- Linker
- Plasma protein binding
- Target protein
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